EryDex for Ataxia Telangiectasia

(OLE_NEAT Trial)

Recruiting at 25 trial locations

Overseen By Pamela Raggi, M.Sc

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Quince Therapeutics S.p.A.

Must not be taking: Systemic corticosteroids

Disqualifiers: Immune impairment, Neoplastic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called EryDex for individuals with ataxia telangiectasia (A-T), a rare genetic disorder affecting movement and coordination. The trial aims to provide EryDex, which uses the steroid dexamethasone sodium phosphate, to patients who participated in a previous study on this treatment. It continues to evaluate EryDex's impact on the neurological symptoms of A-T. Eligible participants are those who completed the earlier study and do not have major immune system issues or require other steroid treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for A-T.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot participate if you require treatment with a systemic corticosteroid (a type of medication that reduces inflammation).

Is there any evidence suggesting that EryDex treatment is likely to be safe for humans?

Previous studies have shown that dexamethasone sodium phosphate, when used with the EryDex System, has a reasonable safety profile for treating patients with ataxia telangiectasia. Common side effects from long-term use include weight gain, a round face, high blood pressure, increased hair growth, and diabetes. These side effects are typically associated with long-term use of glucocorticoids, a group of drugs that includes dexamethasone sodium phosphate.

Research indicates that while these side effects can occur, patients have generally tolerated the treatment well. Potential participants should consult their healthcare providers to understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ataxia telangiectasia?

Unlike the standard treatments for ataxia telangiectasia, which usually focus on managing symptoms and complications with drugs like antibiotics and immunoglobulins, the EryDex treatment uses dexamethasone sodium phosphate (DSP) in a novel way. Researchers are excited about this treatment because it encapsulates DSP in the patient's own red blood cells using the EryDex System, allowing for a controlled and sustained release of the medication. This innovative delivery method might reduce the frequency of administration and minimize side effects typically associated with steroids. By potentially offering a more targeted and efficient approach, this treatment could improve quality of life for patients with ataxia telangiectasia.

What evidence suggests that EryDex might be an effective treatment for ataxia telangiectasia?

Studies have shown that EryDex, which uses dexamethasone sodium phosphate, can help treat ataxia telangiectasia (A-T). This treatment delivers the drug inside red blood cells, potentially reducing side effects and increasing effectiveness. Research indicates that patients have experienced improvements in neurological symptoms. Specifically, the ATTeST study found that EryDex outperformed a placebo in improving the condition of people with A-T. Overall, the evidence supports EryDex as a promising option for those dealing with this rare neurological disorder. ^{1 3 4 6 7}

Who Is on the Research Team?

Dirk Thye, MD

Principal Investigator

Quince Therapeutics S.p.A.

Are You a Good Fit for This Trial?

This trial is for patients with Ataxia Telangiectasia who have completed the IEDAT-04-2022 study. It's an international study, but specific eligibility criteria are not provided.

Inclusion Criteria

Participation in IEDAT-04-2022 study and its completion, including final efficacy and safety assessments

My body weight is at least 15 kg.

Exclusion Criteria

I cannot receive corticosteroid treatment due to immune system issues.

My cancer is active or hasn't been in remission for 2 years.

I need treatment with a steroid medication that affects my whole body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants receive EryDex treatment for ataxia telangiectasia following completion of the NEAT trial

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone sodium phosphate

Trial Overview

The trial provides EryDex (dexamethasone sodium phosphate) to those previously involved in a study assessing its neurological effects on Ataxia Telangiectasia. This extension allows continued access and observation.

How Is the Trial Designed?

Group I: Dexamethasone sodium phosphate Experimental Treatment 1 Intervention

intravenous (IV) infusion of dexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes using the EryDex System (EDS)

Who Is Running the Clinical Trial?

Quince Therapeutics S.p.A.

Lead Sponsor

Trials

10

Recruited

690+

Biotrial

Industry Sponsor

Trials

15

Recruited

1,100+

Published Research Related to This Trial

Dexamethasone implant (Ozurdex™) is generally considered a safe treatment with minimal adverse events, highlighting its favorable safety profile.

The study presents a rare case of a fractured Ozurdex™ implant occurring immediately after injection, providing insights into potential complications and their outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractured dexamethasone implant (OZURDEX®) following intravitreal injection. Aljohani, SM., Al-Shehri, AM., Al-Rubaie, KR.[2021]

In a study of 51 patients receiving paclitaxel (PTX) with aprepitant (APR) and varying doses of dexamethasone (DEX), the incidence of hypersensitivity reactions (HSR) was similar regardless of whether the DEX dose was reduced (51.5% in the higher dose group vs. 53.8% in the lower dose group).

The results indicate that while it is safe to reduce the DEX dose when using APR, this reduction does not decrease the risk of PTX-induced HSR, suggesting that monitoring for adverse effects remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction. Yamamoto, T., Natio, M., Hara, S., et al.[2020]

In a study of 15 patients with non-infectious posterior segment uveitis, the dexamethasone intravitreal implant (Ozurdex) significantly reduced central retinal thickness (CRT) and improved best-corrected visual acuity (BCVA) after the first treatment, with 91.4% of eyes showing CRT reduction and 80% showing BCVA improvement.

The effectiveness of the DEX implant was maintained with repeat use, showing similar improvements in CRT and VA, indicating it can be a valuable adjunct treatment alongside other therapies for managing macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Dexamethasone Implant for the Treatment of Macular Edema in Chronic Non-infectious Uveitis. Tsang, AC., Virgili, G., Abtahi, M., et al.[2018]

The Ozurdex dexamethasone drug delivery system (DDS) is an effective biodegradable implant for treating macular edema associated with retinal vein occlusion and other conditions, providing sustained release of dexamethasone directly to the eye.

While the dexamethasone DDS shows a favorable safety profile, potential side effects include temporary cataract formation and elevated intraocular pressure, which can typically be managed with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dexamethasone drug delivery system: indications and evidence. London, NJ., Chiang, A., Haller, JA.[2022]

The Surodex Drug Delivery System, containing dexamethasone, is a safe and effective method for reducing inflammation after cataract surgery, showing no significant difference in safety compared to conventional dexamethasone eyedrops.

Surodex demonstrated superior efficacy in reducing aqueous flare levels post-surgery, achieving statistically significant reductions at multiple time points, while conventional eyedrops required more steroid augmentation in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of a new dexamethasone delivery system (Surodex) for treatment of post-cataract surgery inflammation. Tan, DT., Chee, SP., Lim, L., et al.[2018]

The mixture of methotrexate and dexamethasone sodium phosphate in 0.9% sodium chloride for intrathecal injection showed excellent stability, with no significant changes in drug concentrations or the appearance of new impurities after mixing.

Visual evaluations and pH monitoring confirmed that the admixture remained clear and stable under normal light conditions, indicating that the two drugs do not negatively affect each other's stability when combined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability and compatibility of methotrexate and dexamethasone in 0.9% sodium chloride for intrathecal injection. Xu, F., Zeng, S.[2021]

In real-life clinical practice, the average number of dexamethasone implant injections for diabetic macular edema (DME) is about 2.4 per year, with an average interval of approximately 4.9 months between treatments, based on data from three studies involving over 700 prescriptions and patient follow-ups.

The consistency in injection frequency across different studies suggests a need for further research to determine the optimal dosing regimen for dexamethasone in treating DME, as current practices may vary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Real-Life Usage of Intravitreal Dexamethasone Implant in the Treatment of Chronic Diabetic Macular Edema in France. Querques, G., Darvizeh, F., Querques, L., et al.[2018]

This study is the first to report that the absolute bioavailability of dexamethasone from topical suspensions is less than 2%, indicating limited effectiveness in reaching the aqueous humor after application.

Intracameral administration of dexamethasone showed a clearance rate of 13.6 µL/min and a volume of distribution of 990 µL, providing valuable pharmacokinetic parameters that can help in designing better ocular delivery systems for dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical pharmacokinetics of dexamethasone suspensions in the rabbit eye: Bioavailability comparison. Naageshwaran, V., Ranta, VP., Toropainen, E., et al.[2022]

The study involving 12 patients and 24 eyes demonstrated that consecutive same-day bilateral intravitreal dexamethasone (Ozurdex) injections are safe and well tolerated, with no complications reported.

This approach may enhance treatment efficiency by reducing the number of patient visits while maintaining safety and clinical effectiveness for conditions like diabetic macular edema and retinal vein occlusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFETY OF CONSECUTIVE SAME-DAY BILATERAL INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX). Kapoor, KG., Colchao, JB.[2021]

Dexamethasone (Dx) can reduce the effectiveness of cisplatin (cDDP) in inducing apoptosis in osteosarcoma cells, decreasing apoptosis by 10-25% when used as a pre or cotreatment.

The protective effect of Dx is linked to the upregulation of the survival factor Akt and a potential direct action on the mitochondrial apoptotic pathway, suggesting that the timing of glucocorticoid administration in cancer treatment should be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. Meyer, S., Eden, T., Kalirai, H.[2020]

Dexamethasone (Dex) significantly reduces the sensitivity of C6 glioma cells to methotrexate (MTX), allowing more cells to survive even at high concentrations of MTX.

This protective effect of Dex was also observed in human TE671 cells, indicating that the interaction between Dex and MTX is not limited to a specific species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. Wolff, JE., Jürgens, H.[2013]

The TROPDEX regimen (tropisetron plus dexamethasone) significantly outperformed the METDEX regimen (metoclopramide, dexamethasone, and diphenhydramine) in preventing acute vomiting in 36 Chinese patients undergoing high-dose cisplatin chemotherapy, achieving complete control in 64% of patients compared to 14% with METDEX.

While TROPDEX was more effective for acute vomiting, both regimens showed similar efficacy in controlling delayed vomiting, and TROPDEX was generally well tolerated, with headache being the most common side effect (27%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial. Chua, DT., Sham, JS., Au, GK., et al.[2022]

In a phase 4 study involving 177 patients with diabetic macular edema (DME), the dexamethasone intravitreal implant (DEX) significantly improved visual acuity, with an average increase of +9.1 letters after the first three injections.

The treatment also led to a substantial reduction in central retinal thickness (CRT) by an average of -137.7 μm, demonstrating its effectiveness in both visual and anatomical outcomes without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study. Singer, MA., Dugel, PU., Fine, HF., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11800360/

Long-term safety of dexamethasone sodium phosphate ...

A phase two study of EryDex in children with ataxia telangiectasia suggested its efficacy (30, 31). Subsequently a large double-blind phase ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39152028/

Safety and efficacy of intra-erythrocyte dexamethasone ...

The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in ...

3.

thelancet.com

thelancet.com/article/S1474-4422(24)00220-5/abstract

Safety and efficacy of intra-erythrocyte dexamethasone ...

The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39917433/

Long-term safety of dexamethasone sodium phosphate ...

The primary objective of this report is to describe the safety of long-term use of EryDex in treatment of pediatric patients with ataxia ...

5.

horizonscandb.pcori.org

horizonscandb.pcori.org/report/topics/943

Encapsulated dexamethasone sodium phosphate in ...

It is intended to treat ataxia telangiectasia, a rare, inherited, childhood-onset neurologic disorder. Ataxia telangiectasia, or Louis-Bar syndrome, is named ...

6.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1526914/full

Long-term safety of dexamethasone sodium phosphate ...

Adverse events typically observed with prolonged glucocorticoid use such as Cushingoid features, weight gain, hypertension, hirsutism, diabetes ...

7.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/07/NCT02770807/Prot_000.pdf

CLINICAL STUDY PROTOCOL

This was a single-arm, open-label, 6-month, Phase II study to assess the effect of the EryDex System end product (EDS-EP; dexamethasone sodium phosphate [DSP] ...